FDA Approves ADI-PEG 20 SPA

Polaris Group announced that the U.S. Food & Drug Administration (FDA) has approved the company’s Special Protocol Assessment (SPA) for a Phase 3 clinical trial of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced hepatocellular carcinoma (HCC). The randomized, placebo-controlled, global trial will enroll approximately 600 patients who have failed prior systemic chemotherapy. The primary endpoint of the study is overall survival.

Ghassan Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center in New York, is the principal investigator of the study.

“ADI-PEG 20 has demonstrated medical benefit in prior studies in multiple indications with a remarkable safety profile,” said Dr. Abou-Alfa. “I am delighted to lead this study to explore ADI-PEG 20 as a viable option for patients with advanced liver malignancies.”

SPA is a mechanism that allows the FDA and drug developers to reach an agreement prior to study initiation about the design and size of a Phase 3 trial. It will form the primary basis of an efficacy claim in a marketing application.

“The SPA agreement with the FDA is a key step in our plans for the clinical development of ADI-PEG 20,” said John Bomalaski, M.D., executive vice president, medical affairs, of Polaris. “We are pleased to move ADI-PEG 20 into a pivotal Phase 3 trial and to be working with such well-established hepatocellular carcinoma experts.”

Leo Chen, M.D., the lead investigator of the Phase 2 HCC study in Taiwan, stated, “Our Phase 2 study demonstrated that ADI-PEG 20 was effective and well-tolerated in patients with advanced liver cancer, and we look forward to the opportunity to further assess the efficacy and safety of this drug in a large randomized Phase 3 study.”

The lead investigator in China, Shukui Qin, M.D., president of the Chinese Society of Clinical Oncology and chair of the Chinese Liver Cancer Study Group, added, “Approximately half of the liver cancer-related deaths in the world are in China. We have been watching the development of this drug, and we are excited to become an active participant in this pivotal global study.”

ADI-PEG 20 is a biologic being developed to treat cancers carrying a major metabolic defect that renders them, unlike normal cells, unable to make arginine internally. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, these cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 works by systemically depleting the external supply of arginine and causes these arginine-dependent cancer cells to die while leaving the normal cells unharmed.

In addition to HCC, multiple other cancers have been reported to have a high degree of arginine-dependency. Early-to-mid-stage clinical trials have yielded positive results in patients with metastatic melanoma, and Phase 2 trials for small cell lung cancer (SCLC) and mesothelioma are currently ongoing. Polaris also plans to initiate clinical studies in prostate cancer, pancreatic cancer, leukemia, lymphoma and sarcoma this year.